1zjk: Difference between revisions
No edit summary |
No edit summary |
||
| (6 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Crystal structure of the zymogen catalytic region of human MASP-2== | ==Crystal structure of the zymogen catalytic region of human MASP-2== | ||
<StructureSection load='1zjk' size='340' side='right' caption='[[1zjk]], [[Resolution|resolution]] 2.18Å' scene=''> | <StructureSection load='1zjk' size='340' side='right'caption='[[1zjk]], [[Resolution|resolution]] 2.18Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1zjk]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[1zjk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZJK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZJK FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.18Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zjk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zjk OCA], [https://pdbe.org/1zjk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zjk RCSB], [https://www.ebi.ac.uk/pdbsum/1zjk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zjk ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
[ | [https://www.uniprot.org/uniprot/MASP2_HUMAN MASP2_HUMAN] Defects in MASP2 are the cause of MASP2 deficiency (MASPD) [MIM:[https://omim.org/entry/613791 613791]. MASPD is a disorder that results in autoimmune manifestations, recurrent severe infections, and chronic inflammatory disease.<ref>PMID:12904520</ref> <ref>PMID:17252003</ref> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/MASP2_HUMAN MASP2_HUMAN] Serum protease that plays an important role in the activation of the complement system via mannose-binding lectin. After activation by auto-catalytic cleavage it cleaves C2 and C4, leading to their activation and to the formation of C3 convertase.<ref>PMID:10946292</ref> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zj/1zjk_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zj/1zjk_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/ | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/ | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1zjk ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
| Line 28: | Line 29: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 1zjk" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Mannan-binding lectin serine protease|Mannan-binding lectin serine protease]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 33: | Line 38: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Ambrus | [[Category: Large Structures]] | ||
[[Category: Balczer | [[Category: Ambrus G]] | ||
[[Category: Barna | [[Category: Balczer J]] | ||
[[Category: Bian | [[Category: Barna L]] | ||
[[Category: Gal | [[Category: Bian T]] | ||
[[Category: Harmat | [[Category: Gal P]] | ||
[[Category: Kocsis | [[Category: Harmat V]] | ||
[[Category: Naray-Szabo | [[Category: Kocsis A]] | ||
[[Category: Sim | [[Category: Naray-Szabo G]] | ||
[[Category: Vegh | [[Category: Sim RB]] | ||
[[Category: Zavodszky | [[Category: Vegh B]] | ||
[[Category: Zavodszky P]] | |||
Latest revision as of 10:45, 30 October 2024
Crystal structure of the zymogen catalytic region of human MASP-2Crystal structure of the zymogen catalytic region of human MASP-2
Structural highlights
DiseaseMASP2_HUMAN Defects in MASP2 are the cause of MASP2 deficiency (MASPD) [MIM:613791. MASPD is a disorder that results in autoimmune manifestations, recurrent severe infections, and chronic inflammatory disease.[1] [2] FunctionMASP2_HUMAN Serum protease that plays an important role in the activation of the complement system via mannose-binding lectin. After activation by auto-catalytic cleavage it cleaves C2 and C4, leading to their activation and to the formation of C3 convertase.[3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedFew reports have described in detail a true autoactivation process, where no extrinsic cleavage factors are required to initiate the autoactivation of a zymogen. Herein, we provide structural and mechanistic insight into the autoactivation of a multidomain serine protease: mannose-binding lectin-associated serine protease-2 (MASP-2), the first enzymatic component in the lectin pathway of complement activation. We characterized the proenzyme form of a MASP-2 catalytic fragment encompassing its C-terminal three domains and solved its crystal structure at 2.4 A resolution. Surprisingly, zymogen MASP-2 is capable of cleaving its natural substrate C4, with an efficiency about 10% that of active MASP-2. Comparison of the zymogen and active structures of MASP-2 reveals that, in addition to the activation domain, other loops of the serine protease domain undergo significant conformational changes. This additional flexibility could play a key role in the transition of zymogen MASP-2 into a proteolytically active form. Based on the three-dimensional structures of proenzyme and active MASP-2 catalytic fragments, we present model for the active zymogen MASP-2 complex and propose a mechanism for the autoactivation process. A true autoactivating enzyme. Structural insight into mannose-binding lectin-associated serine protease-2 activations.,Gal P, Harmat V, Kocsis A, Bian T, Barna L, Ambrus G, Vegh B, Balczer J, Sim RB, Naray-Szabo G, Zavodszky P J Biol Chem. 2005 Sep 30;280(39):33435-44. Epub 2005 Jul 21. PMID:16040602[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||